Does updating improve the methodological and reporting quality of systematic reviews?

BACKGROUND: Systematic reviews (SRs) must be of high quality. The purpose of our research was to compare the methodological and reporting quality of original versus updated Cochrane SRs to determine whether updating had improved these two quality dimensions. METHODS: We identifed updated Cochrane SRs published in issue 4, 2002 of the Cochrane Library. We assessed the updated and original versions of the SRs using two instruments: the 10 item enhanced Overview Quality Assessment Questionnaire (OQAQ), and an 18-item reporting quality checklist and flow chart based upon the Quality of Reporting of Meta-analyses (QUOROM) statement. At least two reviewers extracted data and assessed quality. We calculated the percentage (with a 95% confidence interval) of 'yes' answers to each question. We calculated mean differences in percentage, 95% confidence intervals and p-values for each of the individual items and the overall methodological quality score of the updated and pre-updated versions using OQAQ. RESULTS: We assessed 53 SRs. There was no significant improvement in the global quality score of the OQAQ (mean difference 0.11 (-0.28; 0.70 p = 0.52)). Updated reviews showed a significant improvement of 18.9 (7.2; 30.6 p < .01) on the OQAQ item assessing whether the conclusions drawn by the author(s) were supported by the data and/or analysis presented in the SR. The QUOROM statement showed that the quality of reporting of Cochrane reviews improved in some areas with updating. Improvements were seen on the items relating to data sources reported in the abstract, with a significant difference of 17.0 (9.8; 28.7 p = 0.01), review methods, reported in the abstract 35 (24.1; 49.1 p = 0.00), searching methods 18.9 (9.7; 31.6 p = 0.01), and data abstraction 18.9 (11.7; 30.9 p = 0.00). CONCLUSION: The overall quality of Cochrane SRs is fair-to-good. Although reporting quality improved on certain individual items there was no overall improvement seen with updating and methodological quality remained unchanged. Further improvement of quality of reporting is possible. There is room for improvement of methodological quality as well. Authors updating reviews should address identified methodological or reporting weaknesses. We recommend to give full attention to both quality domains when updating SRs

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

An ATP and Oxalate Generating Variant Tricarboxylic Acid Cycle Counters Aluminum Toxicity in Pseudomonas fluorescens

Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO2-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O2-limited conditions

Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women

Abstract Background PALB2 has recently been identified as a breast cancer susceptibility gene. PALB2 mutations are rare causes of hereditary breast cancer but may be important in countries such as Finland where a founder mutation is present. We sought to estimate the contribution of PALB2 mutations to the burden of breast cancer in French Canadians from Quebec. Methods We screened all coding exons of PALB2 in a sample of 50 French-Canadian women diagnosed with either early-onset breast cancer or familial breast cancer at a single Montreal hospital. The genetic variants identified in this sample were then studied in 356 additional women with breast cancer diagnosed before age 50 and in 6,448 newborn controls. Results We identified a single protein-truncating mutation in PALB2 (c.2323 C>T, resulting in Q775X) in 1 of the 50 high-risk women. This variant was present in 2 of 356 breast cancer cases and in none of 6,440 newborn French-Canadian controls (P = 0.003). We also identified two novel new non-synonymous single nucleotide polymorphisms in exon 4 of PALB2 (c.5038 A>G [I76V] and c.5156 G>T [G115V]). G115V was found in 1 of 356 cases and in 15 of 6,442 controls (P = 0.6). The I76V variant was not identified in either the extended case series or the controls. Conclusion We have identified a novel truncating mutation in PALB2. The mutation was found in approximately 0.5% of unselected French-Canadian women with early-onset breast cancer and appears to have a single origin. Although mutations are infrequent, PALB2 can be added to the list of breast cancer susceptibility genes for which founder mutations have been identified in the French-Canadian population

Glucose-6-Phosphate Dehydrogenase Deficiency in an Endemic Area for Malaria in Manaus: A Cross-Sectional Survey in the Brazilian Amazon

BACKGROUND: There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America. METHODOLOGY/PRINCIPAL FINDINGS: This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewer's test. Gel electrophoresis showed that five of these patients were G6PD A(-). The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure. CONCLUSIONS/SIGNIFICANCE: The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A(-) variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation

Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews

BACKGROUND: Our objective was to develop an instrument to assess the methodological quality of systematic reviews, building upon previous tools, empirical evidence and expert consensus. METHODS: A 37-item assessment tool was formed by combining 1) the enhanced Overview Quality Assessment Questionnaire (OQAQ), 2) a checklist created by Sacks, and 3) three additional items recently judged to be of methodological importance. This tool was applied to 99 paper-based and 52 electronic systematic reviews. Exploratory factor analysis was used to identify underlying components. The results were considered by methodological experts using a nominal group technique aimed at item reduction and design of an assessment tool with face and content validity. RESULTS: The factor analysis identified 11 components. From each component, one item was selected by the nominal group. The resulting instrument was judged to have face and content validity. CONCLUSION: A measurement tool for the 'assessment of multiple systematic reviews' (AMSTAR) was developed. The tool consists of 11 items and has good face and content validity for measuring the methodological quality of systematic reviews. Additional studies are needed with a focus on the reproducibility and construct validity of AMSTAR, before strong recommendations can be made on its use

Competition and habitat quality influence age and sex distribution in wintering rusty blackbirds.

Bird habitat quality is often inferred from species abundance measures during the breeding and non-breeding season and used for conservation management decisions. However, during the non-breeding season age and sex classes often occupy different habitats which suggest a need for more habitat-specific data. Rusty Blackbird (Euphagus carolinus) is a forested wetland specialist wintering in bottomland hardwood forests in the south-eastern U. S. and belongs to the most steeply declining songbirds in the U.S. Little information is available to support priority birds such as the Rusty Blackbird wintering in this threatened habitat. We assessed age and sex distribution and body condition of Rusty Blackbirds among the three major habitats used by this species in the Lower Mississippi Alluvial Valley and also measured food availability. Overall, pecan groves had the highest biomass mainly driven by the amount of nuts. Invertebrate biomass was highest in forests but contributed only a small percentage to overall biomass. Age and sex classes were unevenly distributed among habitats with adult males primarily occupying pecan groves containing the highest nut biomass, females being found in forests which had the lowest nut biomass and young males primarily staying in forest fragments along creeks which had intermediate nut biomass. Males were in better body condition than females and were in slightly better condition in pecan groves. The results suggest that adult males occupy the highest quality habitat and may competitively exclude the other age and sex classes

Prevention and management of malaria during pregnancy: findings from a comparative qualitative study in Ghana, Kenya and Malawi

BACKGROUND: In endemic regions of sub-Saharan Africa, malaria during pregnancy (MiP) is a major preventable cause of maternal and infant morbidity and mortality. Current recommended MiP prevention and control includes intermittent preventive treatment (IPTp), distribution of insecticide-treated bed nets (ITNs) and appropriate case management. This article explores the social and cultural context to the uptake of these interventions at four sites across Africa. METHODS: A comparative qualitative study was conducted at four sites in three countries: Ghana, Malawi and Kenya. Individual and group interviews were conducted with pregnant women, their relatives, opinion leaders, other community members and health providers. Observations, which focused on behaviours linked to MiP prevention and treatment, were also undertaken at health facilities and in local communities. RESULTS: ITNs were generally recognized as important for malaria prevention. However, their availability and use differed across the sites. In Malawi and Kenya, ITNs were sought-after items, but there were complaints about availability. In central Ghana, women saved ITNs until the birth of the child and they were used seasonally in northern Ghana. In Kenya and central Ghana, pregnant women did not associate IPTp with malaria, whereas, in Malawi and northern Ghana, IPTp was linked to malaria, but not always with prevention. Although IPTp adherence was common at all sites, whether delivered with directly observed treatment or not, a few women did not comply with IPTp often citing previous side effects. Although generally viewed as positive, experiences of malaria testing varied across the four sites: treatment was sometimes administered in spite of a negative diagnosis in Ghana (observed) and Malawi (reported). Despite generally following the advice of healthcare staff, particularly in Kenya, personal experience, and the availability and accessibility of medication – including anti-malarials – influenced MiP treatment. CONCLUSION: Although ITNs were valued as malaria prevention, health messages could address issues that reduce their use during pregnancy in particular contexts. The impact of previous side effects on adherence to IPTp and anti-malarial treatment regimens during pregnancy also requires attention. Overtreatment of MiP highlights the need to monitor the implementation of MiP case management guidelines

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic